PROJECT SUMMARY This proposal is a large multi-site site randomized controlled trial evaluating the effectiveness of the newly FDA- approved extended-release buprenorphine formulation (XR-B, SUBLOCADETM) vs. extended-release naltrexone (XR-NTX) among currently incarcerated adult volunteers with moderate-to-severe opioid use disorders (OUD) with an upcoming release date. XR-B may be an effective CJS intervention alongside other OUD medications and may ultimately allow for much wider uptake of opioid agonist medication treatments in CJS populations. High quality effectiveness data for XR-B in CJS is urgently needed. The Multiple PI and Academic CJS partners participating in this consortium will recruit participants from 5 distinct CJS trial sites including: (1) NYU School of Medicine/NYC DOC jail system, (2) Yale/Connecticut DOC, (3) Dartmouth/New Hampshire DOC, (4) Oregon Health & Science University-UCLA/Multnomah County, and (5) Friends Research Institute/Delaware DOC. The PIs and DOC Co-Investigators or collaborators are deeply experienced in working with CJS opioid patient populations and leading high-quality and collaborative NIH clinical trials focused on opioid medication treatments. Trial sites vary considerably, from unified statewide prison/jail systems (CT, DE, NH) to large urban municipal jails (NYC, Portland OR), and with diverse experience with opioid medications as usual care, including methadone (NYC, CT, Portland), SL-B (NYC, CT, DE, Portland), and small XR-NTX pilots (all sites). All of these locations and CJS authorities face unprecedented pressure to contribute CJS-opioid solutions and help reverse the historically high rates of opioid overdose deaths, particularly following release from corrections. A 5-site, open-label, non-inferiority, head-to-head design will randomly assign 666 adult volunteers soon-to-be- released with moderate-to-severe opioid use disorders (OUD) 1:1 to XR-B or XR-NTX in corrections followed by 24-weeks of post-release community treatment, and final long-term follow-up at 12-months. An additional 334 OUD individuals otherwise eligible but not interested in the RCT will be recruited into a quasi-experimental treatment-as-usual 3rd study arm (TAU), for a total recruited sample of N=1,000. Participants will be referred to appropriate community treatment options at Week 24. Final follow-up will occur at Week 52. The primary outcome is retention-in-study medication-treatment during Weeks 1-24 (6 scheduled monthly injections), using a non-inferiority comparison. Secondary outcomes will compare opioid treatment outcomes (e.g. opioid-positive urine samples and self-reported opioid use, other drug/alcohol use, safety events, and HCV, HIV seroconversion). A 3rd non-randomized, quasi-experimental arm of OUD individual (n=334) otherwise eligible but not enrolling in the RCT will allow comparisons with treatment-as-usual (TAU) across the 5 sites.